Copper(?) Complex With Salicylaldehyde Shiff Bases:Synthesis,Structure,Anticancer Properties And Anticancer Mechanism

In this paper,we mainly focuses on the salicylaldehyde Shiff bases(HL1,HL2,HL3,HL4)and its copper(Cu)complexes.Eight new copper complexes have been synthesized and their structures have been characterized by elemental analysis,IR,single-crystal X-ray diffraction analysis.In cellular level,antitumor activity of salicylaldehyde Shiff bases has been examined by MTT assay.Its copper complexes(3,5,6 and 8)against BEL-7404 cells apoptosis induced by them have been examined by flow cytometry(FCM),respectively.In molecular level,the interaction of its copper complexes with apoptosis proteins were investigated by Western Blottin.In conclusion,our results may be helpful to design potentially novel chemotherapeutic agents based on apoptotic pathways.This research is beneficial to the research and development of metal-based antitumor drug.Eight copper[Cu(?)]complexes of the Schiff base ligands(HL1,HL2,HL3,HL4),namely[Cu?2(L1)2(Imidazole)2](1);[Cu?(L1)(Quinoline)(H2O)]H2O(2);[(Cu?)2(L2)2(H2O)(MeOH)](NO3-)2(3);[(Cu?)2(L2)2(H2O)](NO3-)2(4);[(Cu?)(HL2)2](SO42-)·2H2O(5);[(Cu?)(L3)(H2O)]2(SO42-)(6);[(Cu?)2(L3)2(MeOH)][(NO3-)2](7);[(Cu?)(L4)(H2O)]2(NO3-)·H2P·CH3OH(8),were synthesized by step by step reaction and well characterized.Theses complexes(1,3,4,7)crystallize are dimer.Complexes 1,3,4 and 7 crystallize are mononuclear.Complexes 2,5,6 and 8 crystallize are binuclear.The different coordination structures of these copper complexes may contribute to their different antitumor activitie.The antitumor activities of these complexes against a series of human tumor cell lines(A549,NCI-H460,MGC-803,BEL-7404 and HepG2)were screeened by MTT method.The results of experiments indicate that all of these compounds exhibited antitumor activity against all of these cell lines in different degrees.For 3-8 complexes,the inhibition rate to five cancer cell lines can reach more than or close to 50%.Because the chelating of the Cu2+ and ligand demonstrates a synergistic effect,these Cu(?)complexes derived from Schiff base ligands possess high anticancer activities.For complexes(3,5,6 and 8),the apoptosis of cancer cells induced by these Cu(II)complexes may occur via the mitochondrial pathway for producing hydroxyl radicals and reactive oxygen.Furthermore,Cu(II)compounds had a strong influence on pro-and antiapoptotic Bcl-2 family proteins.The results here in reported will provide scientific references and theoretical basis for the design and synthesis of new metal-based antitumor drugs.The antitumor activity of Schiff base ligands as well as its metal-based complexes were discussed.For complexes with remarkable antitumor activity(3,5,6 and 8),internal relationships and the possible influencing factors between antitumor activity and action mechanisms were also discussed.The results here in reported will provide scientific references and theoretical basis for the design and synthesis of new metal-based antitumor drugs.